Effects of chlorpheniramine and hydroxyzine administration, as histamine H1- receptor antagonists, on the nociception threshold of cholestatic rats

The elevated endogenous opioid tone in cholestasis is associated with changes including an increase in the nociception threshold. We aimed to study the effect of chlorpheniramine and hydroxyzine, H1-receptor antagonists, on modulation of nociception in a model of elevated endogenous opioid tone, cholestasis. Cholestasis was induced by ligation of main bile duct using two ligatures and transsection the duct. Tail-flick latencies (TFLs) were measured at 30 minutes after injection of chlorpheniramine (5, 10, 20 and 40 mg/kg, i.p.) and hydroxyzine (6.25, 12.5,25 and 50 mg/kg, i.p.) during 7 days after the surgery. A significant increase (P<0.01) in TFLs was observed in cholestatics compared to non-cholestatics. Chlorpheniramine (10, 20 and 40 mg/kg) and hydroxyzine (12.5, 25 and 50 mg/kg) in cholestatic group significantly increased TFLs compared to saline treated cholestatic group (P<0.05). Drugs injection in noncholestatics did not alter TFLs compared to saline treated ones. These data showed that systemic injection of chlorpheniramine and hydroxyzine modulate nociception threshold in tone, as it does in the increased activity of exogenous opioids. Perhaps, elevation of pain threshold in cholestatic rats is a possible mechanism for the known antipruritic effect of these drugs.